Publications by authors named "Hideyuki Hasegawa"

82 Publications

Advances in ultrasonography: image formation and quality assessment.

J Med Ultrason (2001) 2021 Oct 20;48(4):377-389. Epub 2021 Oct 20.

Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama, 930-8555, Japan.

Delay-and-sum (DAS) beamforming is widely used for generation of B-mode images from echo signals obtained with an array probe composed of transducer elements. However, the resolution and contrast achieved with DAS beamforming are determined by the physical specifications of the array, e.g., size and pitch of elements. To overcome this limitation, adaptive imaging methods have recently been explored extensively thanks to the dissemination of digital and programmable ultrasound systems. On the other hand, it is also important to evaluate the performance of such adaptive imaging methods quantitatively to validate whether the modification of the image characteristics resulting from the developed method is appropriate. Since many adaptive imaging methods have been developed and they often alter image characteristics, attempts have also been made to update the methods for quantitative assessment of image quality. This article provides a review of recent developments in adaptive imaging and image quality assessment.
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http://dx.doi.org/10.1007/s10396-021-01140-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578163PMC
October 2021

A preliminary study on the quantification of soft palate movement using ultrasonography.

Congenit Anom (Kyoto) 2021 Oct 7. Epub 2021 Oct 7.

Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.

Velopharyngeal incompetence (VPI) is a motor impairment of the soft palate that can result in functional disorders, such as stuttering. Therefore, therapeutic interventions for VPI should begin at an early stage. We examined the possibility of early detection of motor impairments of the soft palate with ultrasonographic observations. The study was conducted on five individuals without suckling disorders (two males, three females) at 6-9 postnatal weeks of age (Stage 1) and 13-23 postnatal weeks of age (Stage 2). The extent and speed of soft palate movement during suckling was measured with ultrasonography. The extent of movement of the soft palate was 5.67 ± 0.68 mm at Stage 1 and 6.42 ± 1.55 mm at Stage 2 (t = 0.929, p = 0.190). The speed of soft palate movements at Stage 1 was 44.00 ± 9.93 mm/s during elevation and 27.37 ± 8.07 mm/s during depression (t = 5.182, p = 0.007), whereas that at Stage 2 was 42.89 ± 14.37 mm/s during elevation and 26.43 ± 9.06 mm/s during depression (t = 3.195, p = 0.033). We observed regular soft palate elevations and depressions during suckling. There were no differences in the extent or speed of movements between Stages 1 and 2. Future studies are needed to compare differences in motor impairments of the soft palate between healthy children and those suspected of having a submucous cleft palate or VPI.
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http://dx.doi.org/10.1111/cga.12446DOI Listing
October 2021

Suppression of reflected signals from substrate as clutters for cell measurements using acoustic impedance microscopy.

Ultrasonics 2022 Jan 15;118:106580. Epub 2021 Sep 15.

Honda Electronics Co., Ltd, Toyahashi, Aichi 441-3193, Japan.

Recently, a method for estimating three-dimensional acoustic impedance profiles in cultured cells and human dermal organs was proposed by interpreting the reflected ultrasonic signal based on a 1-D transmission line model for acoustic impedance microscopy (AIM). However, AIM has a disadvantage that reflected signals from cells overlap with that from a reference substrate. Additionally, the amplitudes of the reflected signals from the specimens are significantly weaker than that from the substrate. In this paper, we proposed a new method for separation of those signals based on a concept of clutter filter, which had been developed for a color Doppler method in medical ultrasonic imaging. The proposed filter using singular value decomposition (SVD) could separate original signals into desired signals such as those from the substrate and cells. Additionally, an effect from a tilt of the substrate was investigated in this study. Separability of the proposed filter was evaluated by two investigations. First one was to evaluate the separability by estimating a correlation coefficient between the filtered signal and signal reflected from a position only with the substrate. Second one was to compare a slope of the substrate estimated from the original signal with that estimated from the filtered signals from the substrate. The experimental results showed that the proposed filter could separate signals from the substrate, and the compensation of the tilt of the substrate could improve the performance of the proposed filter.
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http://dx.doi.org/10.1016/j.ultras.2021.106580DOI Listing
January 2022

Correction to: Measurement of flow velocity vectors in carotid artery using plane wave imaging with repeated transmit sequence.

J Med Ultrason (2001) 2021 Oct;48(4):429

Department of Neurology, Nara Medical University, 840 Shijo-cho Kashihara, Nara, 634-8522, Japan.

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http://dx.doi.org/10.1007/s10396-021-01134-xDOI Listing
October 2021

Statistical Analysis of Ultrasonic Scattered Echoes Enables the Non-invasive Measurement of Temperature Elevations inside Tumor Tissue during Oncological Hyperthermia.

Ultrasound Med Biol 2021 Nov 24;47(11):3301-3309. Epub 2021 Aug 24.

Faculty of Engineering, University of Toyama, Toyama, Toyama, Japan.

Non-invasive monitoring of temperature elevations inside tumor tissue is imperative for the oncological thermotherapy known as hyperthermia. In the present study, two cancer patients, one with a developing right renal cell carcinoma and the other with pseudomyxoma peritonei, underwent hyperthermia. The two patients were irradiated with radiofrequency current for 40 min during hyperthermia. We report the results of our clinical trial study in which the temperature increases inside the tumor tissues of patients with right renal cell carcinoma and pseudomyxoma peritonei induced by radiofrequency current irradiation for 40 min could be detected by statistical analysis of ultrasonic scattered echoes. The Nakagami shape parameter m varies depending on the temperature of the medium. We calculated the Nakagami shape parameter m by statistical analysis of the ultrasonic echoes scattered from the tumor tissues. The temperature elevations inside the tumor tissues were expressed as increases in brightness on 2-D hot-scale maps of the specific parameter α, indicating the absolute values of the percentage changes in m values. In the α map for each tumor tissue, the brightness clearly increased with treatment time. In quantitative analysis, the mean values of α were calculated. The mean value of α for the right renal cell carcinoma increased to 1.35 dB with increasing treatment time, and the mean value of α for pseudomyxoma peritonei increased to 1.74 with treatment time. The increase in both α brightness and the mean value of α implied temperature elevations inside the tumor tissues induced by the radiofrequency current; thus, the acoustic method is promising for monitoring temperature elevations inside tumor tissues during hyperthermia.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.07.019DOI Listing
November 2021

Measurement of flow velocity vectors in carotid artery using plane wave imaging with repeated transmit sequence.

J Med Ultrason (2001) 2021 Oct 21;48(4):417-427. Epub 2021 Jul 21.

Department of Neurology, Nara Medical University, 840 Shijo-cho Kashihara, Nara, 634-8522, Japan.

Purpose: Doppler-based methods are widely used for blood flow imaging in clinical settings. However, they inherently estimate the velocity component only in the axial direction. Therefore, various studies of angle-independent methods have been conducted. The multi-angle Doppler method is one such angle-independent method, in which the velocity vector is estimated using axial velocities obtained from multiple directions by steering an ultrasonic beam. Recently, plane wave imaging, which realizes a very high frame rate of several thousand frames per second, was applied to the multi-angle Doppler method. However, the maximum detectable velocity, i.e., the aliasing limit, was reduced depending on the number of steering angles. In the present study, the feasibility of a specific transmit sequence, namely, the repeated transmit sequence, was examined using the plane-wave multi-angle Doppler method.

Method: In the repeated transmit sequence, plane waves were emitted to the same direction twice, after which the steering angle was changed. By repeating the same procedure, a pair of beamformed radio-frequency (RF) signals could be obtained under each beam steering angle. By applying the autocorrelation method to each pair of RF signals, the time interval between the RF signals could be kept as the pulse repetition interval (PRI). The feasibility of such a transmit sequence was examined by numerical simulation and in vivo measurement of a human carotid artery.

Results: The simulation results showed that the maximum steering angles of over 10 degrees were not feasible with the linear array used in the present study. The feasible maximum steering angle would depend on the element pitch of the probe relative to the ultrasonic wavelength. By limiting the maximum steering angles to 5 and 10 degrees, bias errors were 9.2% and 11.3%, respectively, and root mean squared errors were 21.5% and 16.9%, respectively. Also, flow velocity vectors in a human carotid artery could be visualized with the proposed method.

Conclusion: The multi-angle Doppler method was implemented in plane wave imaging with the repeated transmit sequence, and the proposed method was shown to be feasible through numerical simulation and in vivo measurement of a carotid artery.
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http://dx.doi.org/10.1007/s10396-021-01113-2DOI Listing
October 2021

A study on understanding the physical mechanism of change in ultrasonic envelope statistical property during temperature elevation.

Med Phys 2021 Jun 14;48(6):3042-3054. Epub 2021 May 14.

Faculty of Engineering, Academic Assembly, University of Toyama, Gofuku 3190, Toyama, 9308555, Japan.

Purpose: Our previous studies demonstrate that the variation in ultrasonic envelope statistics is correlated with the temperature change inside scattering media. This variation is identified as the change in the scatterer structure during thermal expansion or contraction. However, no specific evidence has been verified to date. This study numerically reproduces the change in the scatterer distribution during thermal expansion or contraction using finite element simulations and also investigates how the situation is altered by different material properties.

Methods: The material properties of a linear elastic solid depend on the thermal expansion coefficient, thermal conductivity, specific heat, and initial scatterer number density. Three-dimensional displacements, calculated in the simulation, were sequentially used to update the positions of the randomly distributed scatterers. Ultrasound signals from the scatterer distribution were generated by simulating a 7.5-MHz linear array transducer whose specifications were the same as those in the experimental measurements of several phantoms and excised porcine livers. To represent the change in the envelope statistical feature, the absolute value of the ratio change in the logarithmic Nakagami (NA) parameter, , at each time was calculated as a value normalized with the initial NA parameter.

Results: The change in the scatterer number density relates to the volume change during temperature elevation. The magnitude of the shift against the temperature change increases depending on the higher thermal expansion coefficient. In contrast, the relationship between and the scatterer number density is similar with any material property. Additionally, the changes in obtained by several experimental phantoms with low to high scatterer number densities are comparable with the numerical simulation results.

Conclusions: The change in is indirectly related to the change in the scatterer number density owing to the volume change during thermal expansion or contraction.
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http://dx.doi.org/10.1002/mp.14890DOI Listing
June 2021

Investigation of feasibility of singular value decomposition clutter filter in plane wave imaging with packet transmission sequence.

J Med Ultrason (2001) 2021 Jan 9;48(1):13-20. Epub 2021 Jan 9.

Department of Neurology, Nara Medical University, 840 Shijo-cho Kashihara, Nara, 634-8522, Japan.

Purpose: Assessment of blood flow is an important function in diagnostic ultrasound imaging. Color flow imaging is one such method widely used in the clinical setting. Since autocorrelation suffers from aliasing, the time interval between successive transmissions of ultrasonic pulses should be as short as possible. For this purpose, a specific transmit-receive sequence, namely, packet transmission, is widely used in color flow imaging. Also, plane wave imaging recently introduced to ultrasound imaging significantly contributes to improvement of the temporal resolution. Furthermore, a singular value decomposition (SVD) clutter filter reportedly outperforms a conventional clutter filter. In the present study, the feasibility of the SVD clutter filter in plane wave imaging with the packet transmission sequence was investigated.

Method: In the present study, the packet transmission sequence was implemented in plane wave imaging by sending plane waves multiple times in the same direction before changing the steering angle. In the first strategy, like conventional color flow imaging with line-by-line acquisition using a focused transmit beam, a clutter filter was applied to ultrasonic radio-frequency (RF) signals in each packet. In the second strategy, the number of transmissions per packet was set at two, and a clutter filter was applied to RF signals obtained from the first or second transmission in different packets.

Results: The in vivo experimental results on a human carotid artery showed that the second strategy with an SVD filter realized significantly better performance than the first strategy with a polynomial regression filter used as a conventional filter.

Conclusion: An SVD clutter filter was feasible in plane wave imaging with the packet transmission sequence, and the performance was improved by limiting the number of transmissions per packet to two.
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http://dx.doi.org/10.1007/s10396-020-01067-xDOI Listing
January 2021

Genetic response to low‑intensity ultrasound on mouse ST2 bone marrow stromal cells.

Mol Med Rep 2021 03 5;23(3). Epub 2021 Jan 5.

Medical Ultrasound Laboratory, Co., Ltd., Tokyo 250‑0014, Japan.

Although low‑intensity ultrasound (LIUS) is a clinically established procedure, the early cellular effect of LIUS on a genetic level has not yet been studied. The current study investigated the early response genes elicited by LIUS in bone marrow stromal cells (BMSCs) using global‑scale microarrays and computational gene expression analysis tools. Mouse ST2 BMSCs were treated with LIUS [I, 25 mW/cm for 20 min with a frequency of 1.11 MHz in a pulsed‑wave mode (0.2‑s burst sine waves repeated at 1 kHz)], then cultured for 0.5, 1 and 3 h at 37˚C. The time course of changes in gene expression was evaluated using GeneChip high‑density oligonucleotide microarrays and Ingenuity Pathway Analysis tools. The results were verified by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). A single exposure of LIUS did not affect cell morphology, cell growth or alkaline phosphatase activity. However, 61 upregulated and 103 downregulated genes were identified from 0.5 to 3 h after LIUS treatment. Two significant gene networks, labeled E and H, were identified from the upregulated genes, while a third network, labeled T, was identified from the downregulated genes. Gene network E or H containing the immediate‑early genes or the heat shock proteins was associated mainly with the biological functions of bone physiology and protein folding or apoptosis, respectively. Gene network T containing transcription factors was also associated with the biological functions of the gene expression. RT‑qPCR indicated that the expression of several genes in the gene networks E and H were elevated in LIUS‑treated cells. LIUS was demonstrated to induce gene expression after short application in mouse ST2 BMSCs. The results of the present study provide a basis for the elucidation of the detailed molecular mechanisms underlying the cellular effects of LIUS.
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http://dx.doi.org/10.3892/mmr.2020.11812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821223PMC
March 2021

Novel Evidence Concerning Lacrimal Sac Movement Using Ultra-High-Frequency Ultrasound Examinations of Lacrimal Drainage Systems.

Ophthalmic Plast Reconstr Surg 2021 Jul-Aug 01;37(4):334-340

Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Ophthalmology, Lund, Sweden.

Purpose: Current hypothesis regarding the mechanism of active tear drainage is based on studies performed ex vivo or under nonphysiological conditions. Novel ultra-high-frequency ultrasound has the advantage of generating images with superior resolution, enabling measurements of low flow in small vessels, and the tracking of tissue motion in real time. The purpose of this study was to investigate the lacrimal drainage system and active drainage using this modality.

Methods: The upper lacrimal drainage system was investigated with 40-70 MHz ultrasound in 22 eyes in 13 patients. Irrigation confirmed a lacrimal obstruction in 10 eyes. Motion tracking was used to map movement of the lateral lacrimal sac wall and to measure flow when possible.

Results: The anatomy of the upper lacrimal drainage system was mapped in vivo, including the proximal canaliculi, which have not previously been imaged. The lacrimal sac lumen is slit shaped in its resting state but is distended when irrigated or if a nasolacrimal duct obstruction is present. Thus, the healthy lacrimal sac is not a cavity, and the medial retinaculum does not act against a stretched structure. Motion tracking visualized the "lacrimal pump," showing that the direction of motion of the lateral lacrimal sac wall is mainly in the sagittal plane during blinking.

Conclusions: Ultra-high-frequency ultrasound allows detailed physiological monitoring of the upper lacrimal drainage system in vivo. Our findings suggest that current theories of active tear drainage need to be reappraised.
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http://dx.doi.org/10.1097/IOP.0000000000001865DOI Listing
July 2021

Preliminary study on the separation of specular reflection and backscattering components using synthetic aperture beamforming.

J Med Ultrason (2001) 2020 Oct 4;47(4):493-500. Epub 2020 Aug 4.

Graduate School of Science and Engineering for Research, University of Toyama, 3190 Gofuku, Toyama, 930-8555, Japan.

Purpose: In the early stages of atherosclerosis, the luminal surface of the arterial wall becomes rough due to injury and detachment of endothelial cells. This roughening can potentially be estimated with ultrasound since the electrical echo signal from the transducer is sensitive to both the angle of incidence to an extended surface as well as the roughness of the surface. Specifically, as the roughness of an interface increases, specular reflection is substituted by scattering. We propose a method that attempts separation of reflection and backscattering components in the received echo signals.

Method: Assuming the predominant propagation directions of the reflected and scattered waves can be somewhat controlled by the emitted sound field, separation of those components was attempted using synthetic aperture imaging with a transmit beam, focused at a point more distant than the imaging depth. Specifically, two dedicated beamforming processes were used for generation of reflection-emphasized and backscattering-emphasized images.

Result: Experimental verifications on a phantom using an ultrasound system with a limited number of active transmit-receive channels yielded a difference between these two images of 8 dB. The results further showed a similar (slightly improved) lateral spatial resolution size of 0.41 mm for the backscattering-emphasized image compared with conventional B-mode imaging (0.47 mm).

Conclusion: A new technique for separation of the reflection and backscattering components using synthetic aperture beamforming with a transmit beam featuring a large focal distance was proposed. The technique demonstrated a partial separation of the reflection and backscattering components, which potentially may be used to estimate surface roughness.
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http://dx.doi.org/10.1007/s10396-020-01038-2DOI Listing
October 2020

Ultrasound measurement of fetal arterial pulse pressure using phased-tracking methods: A phantom study and clinical experience with antenatal corticosteroid therapy.

J Obstet Gynaecol Res 2020 Oct 3;46(10):1994-2001. Epub 2020 Aug 3.

Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan.

Aim: This study aimed to compare the accuracy of fetal pulse pressure estimated with a vascular simulator with that obtained by a manometer (reference) and evaluate the pulse pressure in normal human fetuses and fetuses whose mothers received corticosteroids.

Methods: Fetal pulse pressure was estimated as the product of blood flow velocity and pulse wave velocity, based on the water hammer equation. Ultrasonic raw radiofrequency signals for blood flow velocity were captured from the fetal descending aortas at the diaphragm level, and pulse wave velocity was simultaneously measured from different directions using the phased-tracking method. First, the precision and accuracy of pulse pressure in the estimated method were verified by a circulatory phantom simulator, which reproduced fetal blood flow using a pulsating pump. Then, the pulse pressure of 98 normal human fetuses after 17 weeks of gestation and the fetal pulse pressure in 21 mothers who received antenatal corticosteroids for fetal maturation were measured.

Results: A significant correlation between the estimated pulse pressure values and the actual values was found in the phantom simulation (r = 0.99, P < 0.01). The estimated pulse pressure was significantly correlated with gestational age in normal fetuses (r = 0.74, P < 0.01). In steroid-treated pregnant women, fetal pulse pressure was observed to increase significantly on the second day of administration (P < 0.01).

Conclusion: A noninvasive and accurate estimation model of fetal pulse pressure could be established using phased-tracking method, and this method has the potential to improve the assessment of human fetal hemodynamics.
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http://dx.doi.org/10.1111/jog.14402DOI Listing
October 2020

Feasibility of Non-invasive Pulse Pressure Measurement Using the Phased-Tracking Method.

Ultrasound Med Biol 2020 10 28;46(10):2711-2716. Epub 2020 Jul 28.

Department of Obstetrics and Gynecology, Tohoku University, Sendai, Miyagi, Japan. Electronic address:

Phased tracking (PT) is a high-precision ultrasonic technology that enables measurements of pulse pressure (PP). The aim of this study was to verify the accuracy of estimated PP using PT. Estimated PPs were compared with measured PPs in three sheep fetuses that were connected to an artificial placenta system. Similarly, estimated and measured PPs of 30 human neonates were compared. PP was calculated using the Water-Hammer equation (PP = ρ × PWV (pulse wave velocity) × ΔU). PWV was estimated by measuring the transit times of pulse waves at two sites along the aorta using the PT method, and ΔU was obtained by subtracting end-diastolic velocity from peak systolic velocity. The correlation between the estimated and measured PPs of the sheep fetuses was strong (r = 0.95, p ˂ 0.01), as was the case with the human neonates (r = 0.88, p ˂ 0.05). It can be concluded from the results of this study that PT may be a non-invasive alternative method used to predict PP.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.06.019DOI Listing
October 2020

Temperature elevation in tissue detected in vivo based on statistical analysis of ultrasonic scattered echoes.

Sci Rep 2020 06 3;10(1):9030. Epub 2020 Jun 3.

Faculty of Engineering, Academic Assembly, University of Toyama, 3190 Gofuku, Toyama, Toyama, 930-8555, Japan.

It is demanded to monitor temperature in tissue during oncological hyperthermia therapy. In the present study, we non-invasively measured the temperature elevation inside the abdominal cavity and tumour tissue of a living rat induced by capacitive-coupled radiofrequency heating. In the analysis of ultrasound scattered echoes, the Nakagami shape parameter m in each region of interest was estimated at each temperature. The Nakagami shape parameter m has temperature dependence; hence, the temperature increase inside tissue specimens can be detected with the m values. By carrying out in vivo experiments, we visualized the temperature increase inside the abdominal cavity and tumour tissue of living rats using two-dimensional hot-scale images indicating the absolute values of the ratio changes of the m values. In both the abdominal cavity and tumour tissue, the brightness in the hot-scale images clearly increased with increasing temperature. The increases in brightness in the hot-scale images imply the temperature elevations inside the abdominal cavity and tumour tissue of the living rats. The study results prove that the acoustic method we proposed is a promising method for monitoring changes in the internal temperature of the human body under hyperthermia treatment.
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http://dx.doi.org/10.1038/s41598-020-65562-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270122PMC
June 2020

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway.

PLoS One 2020 1;15(4):e0227393. Epub 2020 Apr 1.

Department of Pediatrics, University of Toyama, Toyama, Japan.

Background: TBX5 is a transcription factor that has an important role in development of heart. TBX5 variants in the region encoding the T-box domain have been shown to cause cardiac defects, such as atrial septal defect or ventricular septal defect, while TBX5 variants have also been identified in a few cardiomyopathy patients and considered causative. We identified a TBX5 variant (c.791G>A, p.Arg264Lys), that is over-represented in cardiomyopathy patients. This variant is located outside of the T-box domain, and its pathogenicity has not been confirmed by functional analyses.

Objective: To investigate whether the TBX5 R264K is deleterious and could contribute to the pathogenesis of cardiomyopathy.

Methods And Results: We developed mice expressing Tbx5 R264K. Mice homozygous for this variant displayed compensated dilated cardiomyopathy; mild decreased fractional shortening, dilatation of the left ventricle, left ventricular wall thinning and increased heart weight without major heart structural disorders. There was no difference in activation of the ANF promotor, a transcriptional target of Tbx5, compared to wild-type. However, analysis of RNA isolated from left ventricular samples showed significant increases in the expression of Acta1 in left ventricle with concomitant increases in the protein level of ACTA1.

Conclusions: Mice homozygous for Tbx5 R264K showed compensated dilated cardiomyopathy. Thus, TBX5 R264K may have a significant pathogenic role in some cardiomyopathy patients independently of T-box domain pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227393PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112173PMC
July 2020

Improvement of performance of minimum variance beamformer by introducing cross covariance estimate.

J Med Ultrason (2001) 2020 Apr 20;47(2):203-210. Epub 2020 Feb 20.

Graduate School of Science and Engineering for Research, University of Toyama, 3190 Gofuku, Toyama, 930-8555, Japan.

Purpose: The delay-and-sum beamformer is widely used in clinical ultrasound systems to obtain ultrasonic images. To improve image quality, the minimum variance (MV) beamformer was introduced in medical ultrasound imaging. The MV beamformer determines beamformer weights from ultrasonic echo signals received by individual transducer elements in an ultrasonic probe. In the present study, the MV beamformer was investigated to improve its performance.

Methods: In MV beamforming, a covariance matrix of echo signals received by individual elements needs to be estimated to obtain adaptive beamformer weights. To obtain a stable estimate, a total receiving aperture is divided into subarrays, and a covariance matrix is obtained using echo signals from each subarray to average covariance matrices from all subarrays. This procedure is called "subarray averaging." In the present study, a new method for estimation of the covariance matrix was proposed. In the proposed method, a covariance matrix, namely, a cross covariance matrix, is obtained using echo signals from different subarrays. Multiple covariance matrices are obtained from all different pairs of subarrays and averaged.

Results: In the present study, the performance of the proposed method was evaluated by basic experiments on a phantom. Lateral spatial resolutions obtained by MV beamforming with conventional subarray averaging and the proposed method were similar. However, contrast obtained by MV beamforming with the proposed method was - 0.56 dB, which was significantly better than the - 5.06 dB obtained by MV beamforming with conventional subarray averaging.

Conclusion: Image contrast in MV beamforming could be improved significantly by estimating "cross" covariance matrices.
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http://dx.doi.org/10.1007/s10396-020-01009-7DOI Listing
April 2020

Low-intensity pulsed ultrasound promotes the expression of immediate-early genes in mouse ST2 bone marrow stromal cells.

J Med Ultrason (2001) 2020 Apr 5;47(2):193-201. Epub 2020 Feb 5.

Medical Ultrasound Laboratory, Co., Ltd., Tokyo, Japan.

Purpose: The effects of low-intensity pulsed ultrasound (LIPUS) on the expression of immediate-early genes (IEGs) in bone marrow stromal cells (BMSCs) were evaluated to elucidate the early cellular response to LIPUS.

Methods: Mouse ST2 BMSCs were treated with LIPUS (I, 12-34 mW/cm for 20 min), then cultured at 37 °C. The expression levels of four IEGs (Fos, Egr1, Jun, and Ptgs2) and ERK1/2, a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), were assessed using real-time quantitative PCR and Western blot analyses, respectively.

Results: A single exposure of LIPUS at an intensity of 25 mW/cm significantly and transiently increased the expression levels of all four IEGs, and the peak expression was detected at 30-60 min after LIPUS stimulation. LIPUS exposure also significantly increased the phosphorylation level of ERK1/2. U0126, an inhibitor of MAPK/ERK, significantly prevented LIPUS-induced expression of Fos and Egr1, but not that of Jun and Ptgs2. On the other hand, treatment of the cells with LIPUS did not affect cell growth or alkaline phosphatase activity, a marker of osteoblast differentiation.

Conclusion: These results suggest that LIPUS exposure significantly induces expression of IEGs such as Fos and Egr1 via the MAPK/ERK pathway in ST2 BMSCs.
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http://dx.doi.org/10.1007/s10396-020-01007-9DOI Listing
April 2020

Modified high-resolution wavenumber analysis for detection of pulse wave velocity using coefficient of variation of arterial wall acceleration waveforms.

J Med Ultrason (2001) 2020 Apr 2;47(2):167-177. Epub 2020 Jan 2.

Graduate School of Science and Engineering for Research, University of Toyama, 3190 Gofuku, Toyama, 930-8555, Japan.

Purpose: In high-resolution wavenumber analysis for detection of pulse wave velocity (PWV), phase information of analytic signals is used to estimate the wavenumber. However, the phase information could be affected by the adjacent signals in the temporal direction. Therefore, we propose a modified high-resolution wavenumber analysis technique using real acceleration waveforms of the arterial wall.

Method: In the modified wavenumber analysis, we propose a new evaluation function that corresponds to the inverse of the squared coefficient of variation. The accuracy of estimation of PWV was investigated by performing simulations, and the feasibility was also examined in an in vivo experiment.

Results: In the simulation experiments, the estimation accuracy using the proposed method was comparable to that using the previous method using phase information. However, when the pulse wave included the reflection components, the PWV estimated using the proposed method was more stable than that estimated using the previous method. Also, in the in vivo experiments, at opening of the aortic valve, the velocity estimated by the proposed method was almost equal to that estimated by the previous method (previous: 2.97 ± 1.2 m/s, proposed: 4.82 ± 1.4 m/s). Meanwhile, when the reflection components were present, the estimated PWV values yielded by the previous and proposed methods were - 1.13 and - 3.50 ± 0.9 m/s, respectively. The PWVs at those two time points estimated by the previous method were quite different, and the PWV estimate was considered to be more affected by the reflected waves.

Conclusion: The results of the simulations and in vivo experiments indicated that the modified high-resolution wavenumber analysis method was less affected by the reflected waves and more accurate in estimation of PWVs of both the forward and reflected waves.
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http://dx.doi.org/10.1007/s10396-019-00998-4DOI Listing
April 2020

Converting Coherence to Signal-to-noise Ratio for Enhancement of Adaptive Ultrasound Imaging.

Ultrason Imaging 2020 01 5;42(1):27-40. Epub 2019 Dec 5.

Graduate School of Science and Engineering, University of Toyama, Toyama, Japan.

High-frame-rate ultrasound is an emerging technique for functional ultrasound imaging. However, the lateral spatial resolution and contrast in high-frame-rate ultrasound with an unfocused transmit beam are inherently lower than those in conventional ultrasonic imaging based on the line-by-line acquisition using a focused ultrasonic beam because of the low directivity of the transmit beam. Coherence-based beamforming methods were introduced in ultrasound imaging for improvement of image quality. Such methods improve the lateral spatial resolution using the coherence among ultrasonic echo signals received by individual transducer elements. In this study, a new method based on the signal-to-noise ratio (SNR) among the element echo signals was developed for enhancement of the effect of the coherence factor (CF), which was previously developed for improvement in spatial resolution and contrast. In the proposed method, a new factor, namely, SNR factor, was introduced, and the relationship between the previously developed CF and SNR factor was discussed. The proposed method was implemented in plane wave imaging, and the performance was evaluated by simulated and phantom experiments. In simulation, the lateral spatial resolution and contrast obtained with the conventional CF were 0.23 mm and 47.0 dB, respectively, which were significantly better than 0.39 mm and 15.3 dB obtained by conventional delay-and-sum (DAS) beamforming. Using the proposed method, the lateral spatial resolution and contrast were further improved to 0.12 mm and 69.8 dB, respectively. Similar trends were found also in phantom experiments.
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http://dx.doi.org/10.1177/0161734619889384DOI Listing
January 2020

Validation of differences in backscatter coefficients among four ultrasound scanners with different beamforming methods.

J Med Ultrason (2001) 2020 Jan 3;47(1):35-46. Epub 2019 Nov 3.

Center for Frontier Medical Engineering, Chiba University, 1-33 Yayoicho, Inage, Chiba, 2638522, Japan.

Purpose: The backscatter coefficient (BSC) indicates the absolute scatterer property of a material, independently of clinicians and system settings. Our study verified that the BSC differed among the scanners, transducers, and beamforming methods used for quantitative ultrasound analyses of biological tissues.

Methods: Measurements were performed on four tissue-mimicking homogeneous phantoms containing spherical scatterers with mean diameters of 20 and 30 µm prepared at concentrations of 0.5 and 2.0 wt%, respectively. The BSCs in the different systems were compared using ultrasound scanners with two single-element transducers and five linear high- or low-frequency probes. The beamforming methods were line-by-line formation using focused imaging (FI) and parallel beam formation using plane wave imaging (PWI). The BSC of each system was calculated by the reference phantom method. The mean deviation from the theoretical BSC computed by the Faran model was analyzed as the benchmark validation of the calculated BSC.

Results: The BSCs calculated in systems with different properties and beamforming methods well concurred with the theoretical BSC. The mean deviation was below ± 2.8 dB on average, and within the approximate standard deviation (± 2.2 dB at most) in all cases. These variations agreed with a previous study in which the largest error among four different scanners with FI beamforming was 3.5 dB.

Conclusion: The BSC in PWI was equivalent to those in the other systems and to those of FI beamforming. This result indicates the possibility of ultra-high frame-rate BSC analysis using PWI.
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http://dx.doi.org/10.1007/s10396-019-00984-wDOI Listing
January 2020

Correction of phase rotation in pulse spectrum method for scanning acoustic microscopy and its application to measurements of cells.

Ultrasonics 2019 Nov 29;99:105949. Epub 2019 Jun 29.

Department of Biomedical Imaging, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8579, Japan.

Scanning acoustic microscopy (SAM) can measure the mechanical properties, such as sound speed, thickness, and density, of biological tissues, by using the pulse spectrum method. However, the estimation method needs to be modified because of increases in the center frequency of acoustic transducers. In this paper, we proposed a new estimation method combining a time-of-flight method by Wiener filtering with the pulse spectrum method. First, an optimal control parameter β for Wiener filter was chosen based on a simulation by k-wave MATLAB toolbox. Setting the thickness of a layer to be 1.95 μm, a bias error between the estimated and true thickness was 0.0016% and the control parameter β was chosen to be 0.01 based on the simulated result and previous research. Next, the thickness of a film sample was measured by the time-of-flight method with Wiener filtering and was compared with an optically-measured thickness to confirm the estimation accuracy. Thickness was estimated to be 18.3 ± 0.025 μm at a center frequency of 120 MHz and agreed with the optically-measured thickness. Finally, the parameter n, the number of phase rotation in Gaussian plane, is calculated from the thickness and sound speed, and the pulse spectrum method with the correction of the parameter n is applied to the cellular measurements. Also, the mechanical properties estimated by the proposed method was compared with these by the conventional method.
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http://dx.doi.org/10.1016/j.ultras.2019.105949DOI Listing
November 2019

Initial phantom study on estimation of speed of sound in medium using coherence among received echo signals.

J Med Ultrason (2001) 2019 Jul 8;46(3):297-307. Epub 2019 Mar 8.

Graduate School of Science and Engineering, University of Toyama, Toyama, 930-8555, Japan.

Purpose: Ultrasound beamforming is required to obtain clinical ultrasound images. In the beamforming procedure, the distance between the receiving focal point and each transducer element is determined based on the assumed speed of sound in the tissue. However, the actual speed of sound in tissue is unknown and varies depending on the tissue type. To improve the performance of an ultrasonic beamformer by evaluating its focusing quality, the coherence factor (CF) was introduced in medical ultrasound imaging. The CF may be used to estimate the speed of sound in tissue because it can identify focusing errors in beamforming. In the present study, the feasibility of CF for estimating the speed of sound was examined through phantom experiments.

Method: To evaluate the dependency of CF on the assumed speed of sound in ultrasound beamforming, beamformed ultrasonic radio frequency (RF) signals and CFs were obtained at different assumed speeds of sound. CF is highest when the assumed speed of sound matches the true speed of sound in the medium. Therefore, the speed of sound in the medium was determined as the assumed speed of sound, which gives the highest CF. The proposed method was validated in a conventional line-by-line sequence with a focused transmit beam and ultrafast plane wave imaging.

Results: A homogeneous phantom (diffuse scattering medium) with a known speed of sound of 1540 m/s was used for validating the proposed method. Beamformed ultrasonic RF signals and CFs were obtained at an assumed speed of sound from 1480 to 1600 m/s varied at a pitch of 5 m/s. In the line-by-line sequence, CF reached the maximum at an assumed speed of sound of 1525.0 m/s (0.97% difference from the true value) when CFs at all spatial points in the region of interest (ROI) were averaged. On the other hand, the speed of sound was determined to be 1528.5 m/s (0.75% difference) when CFs at spatial points with CF-weighted echo amplitudes were larger than 20% of the maximum value. In plane wave imaging, the speed of sound was estimated to be 1544.5 m/s (0.29% difference) using CFs with CF-weighted echo amplitudes larger than 20% of the maximum value.

Conclusion: The speed of sound of a homogeneous medium could be determined by the proposed method with errors of less than 1% using CFs obtained from ultrasonic echo signals selected based on the CF-weighted echo amplitudes, i.e., when echo signals with better signal-to-noise ratios (SNRs) were used.
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http://dx.doi.org/10.1007/s10396-019-00936-4DOI Listing
July 2019

Identification of vascular lumen by singular value decomposition filtering on blood flow velocity distribution.

J Med Ultrason (2001) 2019 Apr 24;46(2):187-194. Epub 2019 Jan 24.

Graduate School of Science and Engineering for Research, University of Toyama, 3190 Gofuku, Toyama, 930-8555, Japan.

Purpose: In the present study, we proposed a novel method for identification of the vascular lumen by employing singular value decomposition (SVD), and the feasibility of the proposed method was validated by in vivo measurement of the common carotid artery.

Method: SVD filtering was applied to a velocity map that was estimated using an autocorrelation method to identify the lumen region. In this study, the packet size was set at 999 frames with a frame rate of 1302 Hz. The region estimated by the proposed SVD filtering was compared with that estimated by the conventional power Doppler method.

Result: The averaged differences in feature values between vascular wall and lumen regions obtained by the proposed and conventional methods were 34 dB and 26 dB, respectively. The proposed method was hardly influenced by the cardiac phase and could separate the wall and lumen regions more stably. The proposed method could identify the lumen region by setting a threshold of - 28 dB from the averaged difference amplitude.

Conclusion: We proposed a novel method for identification of the vascular lumen. The proposed method could suppress the effects of wall motion, which was present in the conventional power Doppler image. The lumen region identified by the proposed method well conformed with the anatomical information in the B-mode image of the corresponding section.
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http://dx.doi.org/10.1007/s10396-019-00928-4DOI Listing
April 2019

Electrochemical polymerization of pyrene and aniline exclusively inside the pores of activated carbon for high-performance asymmetric electrochemical capacitors.

Nanoscale 2018 May;10(20):9760-9772

Department of Applied Chemistry, Aichi Institute of Technology, Yachigusa 1247, Yakusa-cho, Toyota, 470-0392, Japan.

An asymmetric polymer capacitor was prepared from pyrene (PY), aniline (ANI), and commercially available activated carbon (AC) through a solvent-free preparation. PY and ANI were adsorbed into the AC host material in the gas phase and electrochemically polymerized exclusively inside the AC pores in an aqueous H2SO4 electrolyte (1 M). No volumetric expansion of the AC particles occurred upon the adsorption of monomers and their subsequent polymerizations; thus, the volumetric capacitance was enhanced by the inclusion of pseudocapacitive polypyrene (PPY) and polyaniline (PANI). The PPY and PANI structures formed inside the AC pores are very thin and have a large contact area with the conductive carbon surfaces. Therefore, the charge transfer distance between the polymers and the carbon surfaces was drastically shortened, significantly reducing the charge transfer resistance; i.e., high power density. The maximum volumetric capacitances for the PPY- and PANI-hybridized AC reached 314 and 299 F cm-3, respectively. Moreover, the strong adhesion derived from their large contact areas and adsorption capability of AC endow these materials with long cycle lifetimes. The PPY- and PANI-hybridized AC have different redox potentials and can be assembled into an asymmetric capacitor. The volumetric capacitance obtained for the asymmetric capacitor further surpassed that of the symmetric capacitor consisting of pristine AC, with high power density and long cycle lifetimes.
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http://dx.doi.org/10.1039/c8nr01529eDOI Listing
May 2018

Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis.

Diabetes Res Clin Pract 2018 May 15;139:43-51. Epub 2018 Feb 15.

Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address:

Aims: Detection of early-stage atherosclerosis in type 2 diabetes mellitus (T2DM) patients is important for preventing cardiovascular disease. A phased tracking method for evaluating arterial wall elasticity sensitively detects early-stage atherosclerosis. However, biochemical markers for early-stage atherosclerosis have yet to be established.

Methods: This cross-sectional study enrolled 180 T2DM patients, who were classified as not having atherosclerosis according to the carotid intima-media thickness (IMT) criteria. We measured serum cystatin C, the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), and analyzed the associations between these markers and arterial wall elasticity (Eθ), IMT and the cardio-ankle velocity index.

Results: Multiple linear regression analyses revealed that cystatin C was significantly associated with Eθ, while neither eGFR nor ACR showed an association. Furthermore, among the examined atherosclerotic markers, Eθ was most reliably associated with cystatin C. Additionally, the association between cystatin C and Eθ disappeared in the low elasticity subgroup, which included subjects in whom no atherosclerotic changes had yet been initiated.

Conclusions: In T2DM patients without apparent arterial wall thickening, cystatin C is strongly and independently associated with arterial wall elasticity, which reflects the degree of subclinical atherosclerosis. Thus, cystatin C is a potentially useful marker of early-stage atherosclerosis.
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http://dx.doi.org/10.1016/j.diabres.2018.02.003DOI Listing
May 2018

Diagnostic ultrasound widespread.

J Med Ultrason (2001) 2018 Jan;45(1)

Graduate School of Science and Engineering, University of Toyama, Toyama, Japan.

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http://dx.doi.org/10.1007/s10396-017-0843-0DOI Listing
January 2018

Apodized adaptive beamformer.

J Med Ultrason (2001) 2017 Apr 13;44(2):155-165. Epub 2017 Jan 13.

Graduate School of Science and Engineering, University of Toyama, Toyama, 930-8555, Japan.

Purpose: A number of studies aimed at improvement of ultrasound image quality, such as spatial resolution and contrast, have been conducted. Apodization is known as an important factor that determines image quality. However, in the case of amplitude and phase estimation (APES) beamforming, a kind of adaptive beamformer that has been employed in medical ultrasound recently, only rectangular apodization has been used in the previous studies. In this study, apodization was employed in adaptive beamforming, and its effects on image quality were examined in phantom experiments.

Methods: We recently proposed a modified APES beamformer that reduces the computational complexity significantly using sub-aperture beamforming. In this study, the total receiving aperture was divided into four sub-apertures, and the APES beamforming was applied to the output from the four sub-apertures. Before the delay-and-sum (DAS) beamforming in each sub-aperture, echoes received by individual transducer elements were apodized with rectangular, Gaussian, and two Hanning functions, where the apodization with two Hanning functions realized lateral modulation of the ultrasonic field. The lateral spatial resolution was evaluated by the full width at half maximum of an echo from a string phantom, and the image contrast was evaluated using a cyst phantom.

Results: The modified APES beamformer realized a significantly better spatial resolution of 0.38 mm than that of the conventional delay-and-sum beamformer (0.67 mm), even with rectangular apodization. Using Gaussian apodization, the spatial resolution was further improved to 0.34 mm, and contrast was also improved from 4.3 to 5.1 dB. Furthermore, an image obtained by the modified APES beamformer with apodization consisting of two Hanning functions was better "tagged" as compared with the conventional DAS beamformer with the same apodization.

Conclusion: Apodization was shown to be effective in adaptive beamforming, and an image obtained by the adaptive beamformer with lateral modulation seemed to have potential for improvement of the accuracy in measurement of tissue lateral motion.
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http://dx.doi.org/10.1007/s10396-016-0764-3DOI Listing
April 2017

Corticosteroids Mediate Heart Failure-Induced Depression through Reduced σ1-Receptor Expression.

PLoS One 2016 14;11(10):e0163992. Epub 2016 Oct 14.

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, Japan.

Cardiovascular diseases are risk factors for depression in humans. We recently proposed that σ1 receptor (σ1R) stimulation rescued cardiac hypertrophy and heart failure induced by transverse aortic constriction (TAC) in mice. Importantly, σ1R stimulation reportedly ameliorates depression-like behaviors in rodents. Thus, we hypothesized that impaired σ1R activity in brain triggers depression-like behaviors in animals with cardiovascular disease. Indeed, here we found that cardiac hypertrophy and heart failure induced by TAC were associated with depression-like behaviors concomitant with downregulation of σ1R expression in brain 6 weeks after surgery. σ1R levels significantly decreased in astrocytes in both the hippocampal CA1 region and dentate gyrus. Oral administration of the specific σ1R agonist SA4503 (0.3-1.0mg/kg) significantly improved TAC-induced depression-like behaviors concomitant with rescued astrocytic σ1R expression in CA1 and the dentate gyrus. Plasma corticosterone levels significantly increased 6 weeks after TAC, and chronic treatment of mice with corticosterone for 3 weeks elicited depression-like behaviors concomitant with reduced astrocytic σ1R expression in hippocampus. Furthermore, the glucocorticoid receptor antagonist mifepristone antagonized depressive-like behaviors and ameliorated decreased hippocampal σ1R expression in TAC mice. We conclude that elevated corticosterone levels trigger hippocampal σ1R downregulation and that σ1R stimulation with SA4503 is an attractive therapy to improve not only cardiac dysfunction but depression-like behaviors associated with heart failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163992PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065174PMC
June 2017

Improvement of penetration of modified amplitude and phase estimation beamformer.

J Med Ultrason (2001) 2017 Jan 21;44(1):3-11. Epub 2016 Jul 21.

Graduate School of Science and Engineering, University of Toyama, Toyama, 930-8555, Japan.

Purpose: High-frame-rate ultrasound is the predominant technique for the measurement of tissue dynamics. It enables an imaging frame rate of over 1 kHz using unfocused transmit beams and parallel receive beamforming. On the other hand, the spatial resolution is degraded compared to the conventional method based on sequential transmissions of focused beams. For improvement of the spatial resolution of high-frame-rate ultrasound, we have investigated a kind of adaptive beamformer, i.e., amplitude and phase estimation (APES) beamformer.

Method: In our previous study, it was shown that the APES beamformer realized a significantly better spatial resolution than the conventional delay and sum (DAS) beamformer without sub-array averaging and diagonal loading by considering the directivity of each transducer element. By omitting sub-array averaging and adding sub-aperture beamforming, the computational load could also be reduced significantly. One shortcoming of the proposed APES beamformer with element directivity, i.e., modified APES beamformer, is the degradation of penetration compared with the conventional APES beamformer with sub-array averaging and diagonal loading. In the present study, sub-array averaging and diagonal loading were applied to the modified APES beamformer for the improvement of the penetration.

Results: The conventional and modified APES beamformers realized similar performances when used with sub-array averaging and diagonal loading. Furthermore, the modified APES beamformer realized better spatial resolution and improved penetration when used with sub-aperture beamforming and diagonal loading. The modified APES beamformer with diagonal loading at 0.025 of the received power realized a penetration similar to that of the conventional APES beamformer with sub-array averaging and diagonal loading. The lateral spatial resolutions achieved with the conventional and modified APES beamformers were 0.36 and 0.31 mm, respectively. In addition, the modified APES beamformer could reduce the dimension of the covariance matrix to [Formula: see text], versus [Formula: see text] of the conventional APES beamformer, resulting in a computation time of only 1.1 %.

Conclusion: Penetration of the modified APES beamformer could be improved significantly by diagonal loading, which hardly increases the computational complexity.
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http://dx.doi.org/10.1007/s10396-016-0731-zDOI Listing
January 2017

Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction.

J Pharmacol Sci 2016 Jul 4;131(3):172-83. Epub 2016 Jun 4.

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, Japan. Electronic address:

Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R) and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, σ1R expression, mitochondrial Ca(2+) transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca(2+) transport resulting in decreased ATP content by inactivating cardiac σ1R and/or reducing its expression. We also performed transverse aortic constriction (TAC) and then treated mice with haloperidol. After two weeks, haloperidol-treated mice showed enhanced heart failure marked by deteriorated cardiac function, reduced ATP production and increasing mortality relative to TAC only mice. ATP supplementation via sodium pyruvate rescued phenotypes seen in haloperidol-treated TAC mice. We conclude that σ1R inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca(2+) mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation.
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http://dx.doi.org/10.1016/j.jphs.2016.05.012DOI Listing
July 2016
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